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The purpose of this multicenter, dose-ranging study is to compare two Fixed-Dose Combinations of aclidinium bromide and formoterol fumarate with placebo, aclidinium bromide and formoterol fumarate, all administered BID in patients with stable, moderate to severe COPD.
Every treatment period is 14-days long and there is a 7-days wash-out period in between them. The trial starts with a run in phase of 10 to 17-days duration and it ends up with a follow up contact 14-days after last treatment dose.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Formoterol 12 μg | Active Comparator | Formoterol fumarate 12 μg twice daily |
|
| Placebo | Placebo Comparator | Placebo twice daily |
|
| Aclidinium 200 μg / formoterol 12 μg | Experimental | Aclidinium bromide 200 μg + formoterol fumarate 12 μg fixed dose combination (FDC) twice daily |
|
| Aclidinium 200 μg / formoterol 6 μg | Experimental | Aclidinium bromide 200 μg + formoterol fumarate 6 μg fixed dose combination (FDC) twice daily |
|
| Aclidinium 200 μg | Experimental | Aclidinium bromide 200 μg twice daily |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Aclidinium 200 μg / formoterol 12 μg | Drug | Aclidinium bromide 200 μg + formoterol fumarate 12 μg fixed dose combination (FDC) twice daily |
|
| Measure | Description | Time Frame |
|---|---|---|
| Change From Baseline in Normalized Forced Expiratory Volume in 1 Second (FEV1) Area Under the Curve Over 12 Hours (AUC0-12h) After Morning Study Drug Administration at Day 14 | FEV1 was measured via spirometry: 2 sets of tests prior to morning dose separated by 30 minutes, and then 1 set at 30 minutes, 1, 2, 3, 4, 6, 8, 10 and 12 hours post-morning dose | 0 and 30 minutes and 1, 2, 3, 4, 6, 8, 10 and 12 hours post-morning dose at Day 14 |
| Measure | Description | Time Frame |
|---|---|---|
| Change From Baseline in Morning Pre-dose FEV1 at Day 14 | FEV1 was measured via spirometry: 2 sets of tests prior to morning dose separated by 30 minutes | Day 14 |
| Change From Baseline in Morning Peak FEV1 at Day 14 |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Esther Garcia, MD | AstraZeneca | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Research Site | Bucuresti | Czechia | ||||
| Research Site |
Not provided
| Label | URL |
|---|---|
| Almirall Corporate Website | View source |
| CSR Synopsis | View source |
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A total of 176 patients were screened of whom 135 were assessed as eligible and were randomized into the study
There were 41 screen failures, the main reason being non-fulfilment of inclusion/exclusion criteria
This study was conducted at a total of 28 sites (4 sites in Czech Republic, 5 sites in Germany, 3 sites in Hungary, 4 sites in Poland and 12 sites in Romania)
The first patient was screened in February 2010 and the last patient visit was in September 2010
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| ID | Title | Description |
|---|---|---|
| FG000 | Sequence 1 | FDC 200/6 μg - FDC 200/12 μg - Aclidinium 200 μg - Formoterol 12 μg |
| FG001 | Sequence 2 | FDC 200/12 - Aclidinium 200 - Formoterol 12 - Placebo |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Treatment Period 1 |
|
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| Placebo | Drug | Placebo control twice daily |
|
| Formoterol 12 μg | Drug | Formoterol fumarate 12 μg twice daily |
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| Aclidinium 200 μg | Drug | Aclidinium bromide 200 μg twice daily |
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| Aclidinium 200 μg / Formoterol 6 μg | Drug | Aclidinium bromide 200 μg + formoterol fumarate 6 μg fixed dose combination (FDC) twice daily |
|
FEV1 was measured via spirometry: 2 sets of tests prior to morning dose separated by 30 minutes, and then 1 set at 30 minutes, 1, 2, 3, 4, 6, 8, 10 and 12 hours post-morning dose
| 0 and 30 minutes and 1, 2, 3, 4, 6, 8, 10 and 12 hours post-morning dose at Day 14 |
| Constanta |
| Czechia |
| Research Site | Iasi | Czechia |
| Research Site | Tg Mures | Czechia |
| Research Site | Bucharest | Romania |
| Research Site | Cluj-Napoca | Romania |
| Research Site | Deva | Romania |
| Research Site | Iași | Romania |
| Research Site | Oradea | Romania |
| Research Site | Timișoara | Romania |
| FG002 | Sequence 3 | Aclidinium 200 - Formoterol 12 - Placebo - FDC 200/6 |
| FG003 | Sequence 4 | Formoterol 12 - Placebo - FDC 200/6 - FDC 200/12 |
| FG004 | Sequence 5 | Placebo - FDC 200/6 - FDC 200/12 - Aclidinium 200 |
| FG005 | Sequence 6 | FDC 200/6 - Aclidinium 200 - Placebo - FDC 200/12 |
| FG006 | Sequence 7 | FDC 200/12 - Formoterol 12 - FDC 200/6 - Aclidinium 200 |
| FG007 | Sequence 8 | Aclidinium 200 - Placebo - FDC 200/12 - Formoterol 12 |
| FG008 | Sequence 9 | Formoterol 12 - FDC 200/6 - Aclidinium 200 - Placebo |
| FG009 | Sequence 10 | Placebo - FDC 200/12 - Formoterol 12 - FDC 200/6 |
| FG010 | Sequence 11 | FDC 200/6 - Formoterol 12 - FDC 200/12 - Placebo |
| FG011 | Sequence 12 | FDC 200/12 - Placebo - Aclidinium 200 - FDC 200/6 |
| FG012 | Sequence 13 | Aclidinium 200 - FDC 200/6 - Formoterol 12 - FDC 200/12 |
| FG013 | Sequence 14 | Formoterol 12 - FDC 200/12 - Placebo - Aclidinium 200 |
| FG014 | Sequence 15 | Placebo - Aclidinium 200 - FDC 200/6 - Formoterol 12 |
| FG015 | Sequence 16 | FDC 200/6 - Placebo - Formoterol 12 - Aclidinium 200 |
| FG016 | Sequence 17 | FDC 200/12 - FDC 200/6 - Placebo - Formoterol 12 |
| FG017 | Sequence 18 | Aclidinium 200 - FDC 200/12 - FDC 200/6 - Placebo |
| FG018 | Sequence 19 | Formoterol 12 - Aclidinium 200 - FDC 200/12 - FDC 200/6 |
| FG019 | Sequence 20 | Placebo - Formoterol 12 - Aclidinium 200 - FDC 200/12 |
| COMPLETED |
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| NOT COMPLETED |
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| Treatment Period 2 |
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| Treatment Period 3 |
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| Treatment Period 4 |
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| ID | Title | Description |
|---|---|---|
| BG000 | Overall Study Population | All patients randomized into the study |
| Units | Counts |
|---|---|
| Participants |
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| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean | Standard Deviation | Years |
| |||||||||||||||||
| Gender | Count of Participants | Participants |
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| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Change From Baseline in Normalized Forced Expiratory Volume in 1 Second (FEV1) Area Under the Curve Over 12 Hours (AUC0-12h) After Morning Study Drug Administration at Day 14 | FEV1 was measured via spirometry: 2 sets of tests prior to morning dose separated by 30 minutes, and then 1 set at 30 minutes, 1, 2, 3, 4, 6, 8, 10 and 12 hours post-morning dose | Intent to treat (ITT) population: all randomized patients who took at least 1 dose of study drug and had at least 1 baseline and 1 post-baseline assessment of value of FEV1 | Posted | Least Squares Mean | Standard Error | Liters | 0 and 30 minutes and 1, 2, 3, 4, 6, 8, 10 and 12 hours post-morning dose at Day 14 |
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| Secondary | Change From Baseline in Morning Pre-dose FEV1 at Day 14 | FEV1 was measured via spirometry: 2 sets of tests prior to morning dose separated by 30 minutes | Intent to treat (ITT) population: all randomized patients who took at least 1 dose of study drug and had at least 1 baseline and 1 post-baseline assessment of value of FEV1 | Posted | Least Squares Mean | Standard Error | Liters | Day 14 |
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| Secondary | Change From Baseline in Morning Peak FEV1 at Day 14 | FEV1 was measured via spirometry: 2 sets of tests prior to morning dose separated by 30 minutes, and then 1 set at 30 minutes, 1, 2, 3, 4, 6, 8, 10 and 12 hours post-morning dose | Intent to treat (ITT) population: all randomized patients who took at least 1 dose of study drug and had at least 1 baseline and 1 post-baseline assessment of value of FEV1 | Posted | Least Squares Mean | Standard Error | Liters | 0 and 30 minutes and 1, 2, 3, 4, 6, 8, 10 and 12 hours post-morning dose at Day 14 |
|
Up to 14 days following last dose of the investigational medicinal product (given over 14±2 days of treatment per period, with 4 treatment periods per patient)
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Placebo | Placebo twice daily | 0 | 101 | 0 | 101 | ||
| EG001 | Aclidinium 200 μg / Formoterol 12 μg | Aclidinium bromide 200 μg + formoterol fumurate 12 μg fixed dose combination (FDC) twice daily | 2 | 101 | 0 | 101 | ||
| EG002 | Aclidinium 200 μg / Formoterol 6 μg | Aclidinium bromide 200 μg + formoterol fumurate 6 μg fixed dose combination (FDC) twice daily | 0 | 102 | 0 | 102 | ||
| EG003 | Aclidinium 200 μg | Aclidinium bromide 200 μg twice daily | 0 | 100 | 0 | 100 | ||
| EG004 | Formoterol 12 μg | Formoterol fumurate 12 μg twice daily | 1 | 101 | 0 | 101 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Pulmonary mass | Respiratory, thoracic and mediastinal disorders | MedDRA v13 | Systematic Assessment |
| |
| Chronic obstructive pulmonary disease | Respiratory, thoracic and mediastinal disorders | MedDRA v13 | Systematic Assessment |
| |
| Ventricular tachycardia | Cardiac disorders | MedDRA v13 | Systematic Assessment |
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Publication and/or presentation whether complete or partial, of any part of the data or results of this trial will be subject to revision and written agreement between the investigator and sponsor
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Study Director | AstraZeneca | ClinicalTrialTransparency@astrazeneca.com |
| ID | Term |
|---|---|
| D029424 | Pulmonary Disease, Chronic Obstructive |
| D001991 | Bronchitis |
| D000092122 | Bronchiolitis Obliterans Syndrome |
| D004646 | Emphysema |
| ID | Term |
|---|---|
| D008173 | Lung Diseases, Obstructive |
| D008171 | Lung Diseases |
| D012140 | Respiratory Tract Diseases |
| D002908 | Chronic Disease |
| D020969 | Disease Attributes |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D012141 | Respiratory Tract Infections |
| D007239 | Infections |
| D001982 | Bronchial Diseases |
| D000092124 | Organizing Pneumonia |
| D001989 | Bronchiolitis Obliterans |
| D001988 | Bronchiolitis |
| D006086 | Graft vs Host Disease |
| D007154 | Immune System Diseases |
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| ID | Term |
|---|---|
| C542859 | aclidinium bromide |
| D000068759 | Formoterol Fumarate |
| ID | Term |
|---|---|
| D004983 | Ethanolamines |
| D000605 | Amino Alcohols |
| D000438 | Alcohols |
| D009930 | Organic Chemicals |
| D000588 | Amines |
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| Withdrawal by Subject |
|
| Withdrawal by Subject |
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| Mixed Models Analysis |
Treatment and period as fixed effects, subject as random effect, and baseline values at each period as a covariate |
| <0.0001 |
| Least squares mean difference |
| 0.234 |
| Standard Error of the Mean |
| 0.024 |
| 2-Sided |
| 95 |
| 0.186 |
| 0.281 |
| No |
| Superiority or Other |
| Formoterol 12 μg |
Formoterol fumurate 12 μg twice daily |
|
|
| OG004 | Formoterol 12 μg | Formoterol fumurate 12 μg twice daily |
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